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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-12-3629.
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Blood, 15 July 2003, Vol. 102, No. 2, pp. 470-476
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin–based reduced-intensity preparative regimen
Mohamad Mohty,
Jacques-Olivier Bay,
Catherine Faucher,
Bachra Choufi,
Karin Bilger,
Olivier Tournilhac,
Norbert Vey,
Anne-Marie Stoppa,
Diane Coso,
Christian Chabannon,
Patrice Viens,
Dominique Maraninchi, and
Didier Blaise
From the Unité de Transplantation et de Thérapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille; Unité de Transplantation Médullaire, Centre Jean-Perrin, Clermont-Ferrand; Département d'Hématologie, Institut Paoli-Calmettes and Université de la Méditerranée, Marseille; Centre de Thérapie Cellulaire et Génique (CTCG), Institut Paoli-Calmettes, Marseille; and Département d'Oncologie Médicale, Institut Paoli-Calmettes and Université de la Méditerranée, Marseille, France.
Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantation-related mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P = .0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P = .0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n = 69) and without (n = 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P = .02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.
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